Dr. Ian Wood discusses the potential role of epigenetics in chronic disease development. This short take was shot during a break at Keystone Symposia’s meeting on Environmental Epigenomics and Disease Susceptibility held in March 2011 in Asheville, North Carolina.
Epigenetics in Chronic Disease
So my research group, we’re interested in the mechanisms that are responsible for initiating and maintaining chronic disease states. So a good example would be most of the cardiovascular diseases are chronic diseases.
So a lot of these chronic diseases are initiated by some small trauma or perturbation that on its own doesn’t have any obvious affect, but it develops and accumulates over time until eventually an individual then presents to their doctor with some clinical problem.
Now we think epigenetics is actually the center of a lot of these chronic disease states, and they’re a very good mechanism by which these chronic diseases can be maintained over long times. So we know that epigenetic marks can be taken off or added on just in some periods the result of a trauma or insult. And they’re persistent, and they self-mutate long after the trauma is gone. So we think, to us at least, understanding the epigenetics is key to understanding the chronic disease states.
So we’re particularly focused on understanding the mechanisms that are important for generating the epigenetics marks, the DNA methylation, or the modifications that occur on histones or removing those marks.
So to give you an example, one of the projects we’re currently working on is we’re looking at diabetics. Diabetic individuals, or individuals with diabetes, are much more prone to cardiovascular disease than individuals who are not diabetic. We’ve got some good evidence that there’s some epigenetic mechanisms that underlie that.
“…we think epigenetics is actually the center of a lot of these chronic disease states, and they’re a very good mechanism by which these chronic diseases can be maintained over long times.”
So, for example, we can take cells from blood vessels from diabetic individual, and from non-diabetic individual, and we can culture those in our laboratory. And when we do that we can see that the cells from the diabetic individual, they grow bigger and they’re more robust – they divide and they grow faster.
So these cells are from individuals who have acquired diabetes as part of their lifestyle, so the difference in their cells is not due to a genetic difference, but it must be an acquired difference. And because it’s maintained over cell divisions, presume that’s an epigenetic effect. So we’re trying to understand what the epigenetic difference is between the diabetic cells compared to the cells from a non-diabetic individual, and hopefully we can make some progress at least in treating those individuals.
So epigenetic marks have been proposed to be a code, or a language, and over the last few years our understanding of how the letters of that code are put down, and what those letters are has progressed dramatically. But we’re still really unsure about how those letters come together to form a word, and when those letters do form a word what they actually mean to the cell. So we’re hoping that the things that we’re doing, and other groups, will hopefully give us a better understanding to decipher what the language is so we understand what the words mean, and are telling us about what the cell state is.
Once we get the important marks – the marks that drive the disease, because all of those marks are either put down or taken off by proteins or enzymes, and because enzymes are actually very amenable to targeting by small pharmaceutical drugs, hopefully then we can start to develop some new therapies that will actually target those enzymes and modify the epigenetic state.